Then I can point to an example of macroevolution. We can find mutations in pocket mice that produced an increase in functional information. This gain of function mutation allows mice to have black fur:

"Both alleles of the entire Mc1r gene (954 bp) were sequenced in the 69 mice in Fig. 1. Twenty-four single-nucleotide polymorphisms were observed: 15 were synonymous and 9 were nonsynonymous. Four of the nine amino acid polymorphisms were observed only in the dark mice from the Pinacate locality (Arg-18 ¡ú Cys, Arg-109 ¡ú Trp, Arg-160 ¡ú Trp, and Gln-233 ¡ú His). These four amino acid variants were present at high frequency (82%) among the Pinacate dark mice and were in complete linkage disequilibrium with one another. All other Mc1r amino acid polymorphisms were present at low frequencies and showed no association with mouse color. "

"Third, the dark allele is dominant over the light allele, consistent with observations of Mc1r mutations in the mouse (11, 16) and other organisms (21¨C25). In the laboratory mouse, loss-of-function mutations at Mc1r are recessive and result in light color, whereas gain-of-function alleles are dominant and result in dark color (16). All heterozygous mice observed at the Pinacate site are dark with unbanded hairs and are phenotypically similar to the homozygous dark mice. "http://www.pnas.org/content/100/9/5268.full

Possibly; at least in the Pinacate population since different results were obtained in the Armendaris population.

I'm not sure how they define gain-of-function mutations except as they relate to colour. This is not necessarily the same as a gain of functional information. A broken switch can result in a light that is always on or always off, but the switch is still broken. Since "This difference is controlled in large part by the interaction of two proteins, the melanocortin-1-receptor (MC1R) and the agouti-signaling protein" the mutations could prevent normal interaction of this system; the equivalent to a broken switch.

Remember that beneficial is not the same as an increase in functional information. As has been found in bacteria a mutation that disables a normal function can be beneficial if it also prevents an antibiotic from working. A loss of pigmentation in the hair of polar bears has been beneficial to them.

Only 4 of the mutations are associated with the dark colour and it has not been established yet how many of these are actually producing the result, with the other piggy-backing.

A comparison could be with Nylonase which has been shown to be a fine tuning of an existing enzyme that already had some action on nylon, and this is acknowledged to be within the capability of the mutation-selection mechanism. As Douglas Axe said Darwinism is a good tinkerer but a poor innovator.

Whether this is actually a statistically significant increase in functional information I have neither the skills or resources to determine. So I will say again; Possibly.

btw, I take it then that you have accepted Durston's definitions for micro and macro evolution.

I'm not sure how they define gain-of-function mutations except as they relate to colour. This is not necessarily the same as a gain of functional information. A broken switch can result in a light that is always on or always off, but the switch is still broken. Since "This difference is controlled in large part by the interaction of two proteins, the melanocortin-1-receptor (MC1R) and the agouti-signaling protein" the mutations could prevent normal interaction of this system; the equivalent to a broken switch.

It's automatically a gain of functional information because there's a new function in the population, but it hasn't gone to fixation and replaced the old. Mice of two different colours require more functional information than monochrome mice.

However, you cannot quantify the new functional information in the way suggested in the Hazen/Szostak paper you linked to here in full unless you know the proportion of all proteins of the Mc1r length that would produce the function "dark mouse".

More likely a loss of function since the interaction between the melanocortin-1-receptor (MC1R) and the agouti-signaling protein has been lost.

There's more functional information in the population as a whole if both light and dark mice are present than if there's just one colour. However, whether one color group or the other has the higher (Hazen paper) functional information content would be determined by what proportion of all proteins (of that size) could perform the same function. If the proportion that could give "dark" was higher than that for "light", dark would have lower functional information, and vice versa.

So, if the new dark allele went to fixation, we'd need more information to tell us whether there would have been an increase or decrease in "Hazen/Szostak" functional information.

CRR writes:

You accept then that it is in principal possible to measure genetic functional information in at least some cases.

As defined by Hazen/Szostak, "functional information" in general, yes. In individual English words that have only one meaning, it could be measured by counting the synonyms. The more synonyms, the less functional information. It's difficult for coding genes/proteins in practical terms, because of the difficulties of finding out what proportion of random sequences would perform the function.

Szostak and Co. have attempted it for the function of ATP binding, and came up with an estimate of 1 in ~10^11 for functional proteins. If that kind of figure applied to performing a mouse Mc1r function, you can imagine the difficulties of actually trying out 10^12 or more random sequences in order to get a statistically significant percentage one way or the other for "dark" and "light". Whichever has the highest percentage would be the set of alleles with the least Hazen functional information content, like the words with the most synonyms.

Szostak's ~1 in 10^11 estimate is in keeping with the evidence that new coding genes do form from random "junk", as well as by neo-functionlization on duplicates of existing genes.

If the arrival of new genes via mutations isn't "statistically significant", then "statistically significant" information would never have been required in our life system. Macro-evolution by your chosen definition wouldn't be necessary.

So, what is statistically significant?

Kirk Durston makes the mistake of assuming that only proteins in an existing protein family will perform a given function, then estimating the variants of that family that would perform the function, then subtracting that from the total of all sequences. That's a good way of getting a very low proportion of the total, and therefore very high "functional information" content. That is then made into an improbability argument against evolution which appears to convince some creationists, but not biologists who know that unrelated proteins can perform the same functions.

He would probably regard a new functional protein as being statistically significant if less than 1 in 10^43 random sequences could produce the function (that figure's based on estimates of the total mutations to have taken place in our life system). In which case, there's no reason to believe that macro-evolution, by his definition, has ever been required in this life system or would be in any other protein based life system.

This is NOT a new gene. This is at best a new allele of the existing MC1R gene.

I didn't say it was a new gene. Try my post again, and you'll see that the reference to new genes was in relation to the production of additional genes by de novo formation from "junk" or duplication and neo-functionalization. I'd moved on to the crux of the issue!

CRR writes:

It is also probably a defective version of the existing MC1R as I've already said.

"Defective" would mean producing a disadvantaged phenotype, and the two phenotypes are advantageous or disadvantageous depending on the two environments, so neither allele is objectively defective.

The Hazen/Szostak measurement of functional information in the new "dark mouse" allele would be arrived at by establishing what proportion of random protein sequences could be inserted to produce the "dark mouse" function. If that was known, it can be inserted into their formula and divided into the total of sequence space to give the functional information value. That would then be the measure of functional information increase while both alleles remained in the population, but that does not mean that the dark mice have more functional information than the light ones, or the other way around, as I tried to explain in the first post.

Adding new functional genes (increasing their quantity) is what usually interests creationists, because it would be part of the necessary increase in functional information from organisms with a handful of coding genes to modern complex eukaryotes that can have tens of thousands. So that's why I skipped ahead.

That's what people like Kirk Durston are interested in, and that's what he is trying to make his definition of micro-evolution to exclude, and describe as macro-evolution, which he argues is impossible.

Incorrect. Defective means no longer performing the original function, nor an improved one". Many cases of antibiotic resistance come from a defect that disables a feature, such as a binding site, that the antibiotic needs to be effective.

In the mouse case the new allele is defective since the interaction with the agouti-signaling protein no longer works. It is a defect but the result is beneficial when the mouse lives in the dark lava fields. However it is a disadvantage on the lighter coloured sand. Benefit depends on environment.

Possibly; at least in the Pinacate population since different results were obtained in the Armendaris population.

The phenotypic results were the same in the form of a dominant allele for dark fur color. As the previous post states, a dominant black allele for coat color is a gain in function.

I'm not sure how they define gain-of-function mutations except as they relate to colour. This is not necessarily the same as a gain of functional information. A broken switch can result in a light that is always on or always off, but the switch is still broken.

A mutation that changes gene expression is a gain in functional information.

I would bet $100 dollars that if the switch were on all of the time and then a mutation caused the switch to turn off and on, you would call that a loss in functional information as well. Am I wrong? It would seem that no matter what change is made you will call it a loss in functional information. If a fish evolves limbs you will call that a loss in information because it no longer has fins.

Be honest, there is no evidence that you will ever accept as a gain in functional information.

Since "This difference is controlled in large part by the interaction of two proteins, the melanocortin-1-receptor (MC1R) and the agouti-signaling protein" the mutations could prevent normal interaction of this system; the equivalent to a broken switch.

And there we have it. If a fish evolved limbs from fins, you would claim that it is equivalent to a broken switch because it is normal for the fish to have fins. You classify all changes as broken switches simply because they are a change.

Remember that beneficial is not the same as an increase in functional information.

Then evolution doesn't need to produce functional information in order to produce macroevolution as you define it. If we started with the earliest vertebrate and watched ever generation from that ancestor to modern humans you would classify the whole thing as a continual loss of information simply because the organisms change.

A comparison could be with Nylonase which has been shown to be a fine tuning of an existing enzyme that already had some action on nylon, and this is acknowledged to be within the capability of the mutation-selection mechanism. As Douglas Axe said Darwinism is a good tinkerer but a poor innovator.

Yet another invocation of "fine tuning" to get out of admitting there was a gain in functional information. "Fine tuning" is just a nonsense word you have made up.

btw, I take it then that you have accepted Durston's definitions for micro and macro evolution.

As we have already seen, you have already stopped using those definitions.

Defective means no longer performing the original function, nor an improved one".

The problem is that you define any change as a defect no matter how beneficial that change is. Once again, you would label every single evolutionary change from the first vertebrate ancestor to modern humans as a continual loss in function simply because the organisms didn't do what they used to do.